PROTEASE CLEAVAGE OF REOVIRUS CAPSID PROTEIN MU-1 MU-1C IS BLOCKED BYALKYL SULFATE DETERGENTS, YIELDING A NEW-TYPE OF INFECTIOUS SUBVIRIONPARTICLE/

Mammalian reovirus virions undergo partial disassembly of the outer ca psid upon exposure to proteases in vitro, producing infectious subviri on particles (ISVPs) that lack protein sigma 3 and contain protein mu 1/mu 1C as endoprotease-generated fragments mu 1 delta/delta and phi. ISVPs are thought to be required for two early steps in reovirus infec tion: membrane penetration and activation of the particle-bound viral transcriptase complexes. Genetic and biochemical evidence implicates o uter-capsid protein yl in both these steps. To determine whether the c leavage of mu 1/mu 1C is relevant to the unique properties of ISVPs, w e analyzed the properties of novel subvirion particles that lacked sig ma 3 yet retained mu 1/mu 1C in an uncleaved but cleavable form. These detergent-plus-protease subvirion particles (dpSVPs) were produced by treating virions with chymotrypsin in the presence of micelle-forming concentrations of alkyl sulfate detergents. Infections with dpSVPs in murine L or canine MDCK cells provided evidence that the cleavage of mu 1/mu 1C during viral entry into these cells is dispensable for reov irus infection. Additionally, dpSVPs behaved like ISVPs in their capac ity to permeabilize lipid bilayers and to undergo transcriptase activa tion in vitro, supporting the conclusion that cleavage of mu 1/mu 1C t o mu 1 delta/delta and phi during viral entry is not required for eith er membrane penetration or transcriptase activation in cells. The capa city of alkyl sulfate detergents to inhibit the cleavage of mu 1/mu 1C in a reversible fashion suggests a specific association between virus particle and detergent micelles that may mimic virus particle-phospho lipid membrane interactions during reovirus entry into cells.